Journal
ANTIOXIDANTS
Volume 11, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/antiox11050838
Keywords
omega-3 fatty acids; docosahexaenoic acid; curcumin; Alzheimer's disease; amyloid-beta peptide; intranasal; microemulsion; cognitive impairment; Tau protein
Funding
- INSERM
- University of Montpellier
- EPHE annual resources (France)
- Agence Nationale de la Recherche under the program Investissements d'Avenir (LabEx LipSTIC) [ANR-11-LABX-0021]
- Region Bourgogne FrancheComte
- Fonds Europeen de Developpement Regional
- Region Occitanie
- SATT AxLR
- University of Montpellier, France (CBS2 Ph.D.program)
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Polyunsaturated fatty acids (PUFAs), especially DHA, play a crucial role in brain development and function. Low levels of DHA have been associated with cognitive impairment and AD. The relationship between dietary DHA intake and cognitive decline remains inconclusive. The oxidizability of DHA and its limited accessibility to the brain may contribute to these inconsistencies. New strategies to enhance DHA supply to the brain are needed.
Polyunsaturated fatty acids (PUFAs) are a class of fatty acids that are closely associated with the development and function of the brain. The most abundant PUFA is docosahexaenoic acid (DHA, 22:6 n-3). In humans, low plasmatic concentrations of DHA have been associated with impaired cognitive function, low hippocampal volumes, and increased amyloid deposition in the brain. Several studies have reported reduced brain DHA concentrations in Alzheimer's disease (AD) patients' brains. Although a number of epidemiological studies suggest that dietary DHA consumption may protect the elderly from developing cognitive impairment or dementia including AD, several review articles report an inconclusive association between omega-3 PUFAs intake and cognitive decline. The source of these inconsistencies might be because DHA is highly oxidizable and its accessibility to the brain is limited by the blood-brain barrier. Thus, there is a pressing need for new strategies to improve DHA brain supply. In the present study, we show for the first time that the intranasal administration of nanovectorized DHA reduces Tau phosphorylation and restores cognitive functions in two complementary murine models of AD. These results pave the way for the development of a new approach to target the brain with DHA for the prevention or treatment of this devastating disease.
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